Multiple hydrogen-bonded dimers: are only the frontier atoms relevant?

Non-frontier atom exchanges in hydrogen-bonded aromatic dimers can induce significant interaction energy changes (up to 6.5 kcal mol). Our quantum-chemical analyses reveal that the relative hydrogen-bond strengths of -edited guanine-cytosine base pair isosteres, which cannot be explained from the frontier atoms, follow from the charge accumulation in the monomers.

Lessons for Oral Bioavailability: How Conformationally Flexible Cyclic Peptides Enter and Cross Lipid Membranes.

Cyclic peptides extend the druggable target space due to their size, flexibility, and hydrogen-bonding capacity. However, these properties impact also their passive membrane permeability. As the "journey" through membranes cannot be monitored experimentally, little is known about the underlying process, which hinders rational design.